Abstract
Stromal cells of the tumor microenvironment have been shown to play important roles in both supporting and limiting cancer growth. The altered phenotype of tumor-associated stromal cells (fibroblasts, immune cells, endothelial cells etc.) is proposed to be mainly due to epigenetic dysregulation of gene expression; however, only limited studies have probed the roles of epigenetic mechanisms in the regulation of stromal cell function. We review recent studies demonstrating how specific epigenetic mechanisms (DNA methylation and histone post-translational modification-based gene expression regulation, and miRNA-mediated translational regulation) drive aspects of stromal cell phenotype, and discuss the implications of these findings for treatment of malignancies. We also summarize the effects of epigenetic mechanism-targeted drugs on stromal cells and discuss the consideration of the microenvironment response in attempts to use these drugs for cancer treatment.
Acknowledgements
We would like to acknowledge the contributions of the authors of the excellent research studies and comprehensive reviews that were cited herein. We apologize to any authors whose work we omitted due to space limitations.
Financial & competing interests disclosure
This work was supported by the NIH/NCI CA136526, Mayo Clinic Pancreatic SPORE P50 CA102701, and Mayo Clinic Center for Cell Signaling in Gastroenterology P30 DK84567 to ME Fernandez-Zapico. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.